The present proposal is undertaken to delineate the cellular mechanism causing metabolic derangements in the myocardium in diabetic state in order to clarify the role of the heart in pathogenesis of diabetes mellitus, particularly as related to various cardiovascular disorders. The proposed experiments involve the following aspects: 1) the membrane binding properties of isolated heart myocytes to insulin, catecholamines, and glucagon; 2) the transport of metabolites such as FFA, lactate, glucose, and amino acids across the plasma membrane of isolated adult cardiac muscle cells; 3) the oxidation of FFA, lactate, and glucose by cardiac muscle cells; 4) the incorporation of fatty acid precursor into myocardial phospholipid, triglyceride, and cholesterol; 5) the rate-limiting reactions in the glycolytic pathway and TCA cycle as well as the long-chain fatty acid oxidation pathway; 6) the changes in hemodynamic parameters and contractile properties of ventricular papillary muscles. The controlling mechanisms involved in the above mentioned studies in non-diabetic and diabetic myocardium will be elucidated. Once the controlling mechanism in metabolic defects in the myocardium is determined, we will attempt to prevent or delay the progression of these defects by means of pharmacological interventions.